Primary contact

ORCID ID

Contact details

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Neu-2566-HV-001

Study information

Scientific title

Acronym

Study hypothesis

Based on pre-clinical studies, NNZ-2566 is shown to have the potential to prevent the neurological damage that can occur as a result of the traumatic brain injury. Objectives of this study are:1. To determine the safety and tolerability of a single intravenous dose of NNZ 2566 in healthy volunteers when administered as a 10-minute infusion2. To determine the single dose pharmacokinetics of NNZ-2566 after a 10-minute infusion

Ethics approval

Ethics approval received from the Alfred Ethics Committee on the 13th February 2006 (ref: 7/06).

Study design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Traumatic brain injury

Intervention

Subjects will undergo screening to confirm eligibility. Subsequently, subjects will be admitted to the clinical facility for administration of either placebo or the active drug in a 2:5 fashion in each of the five cohorts. This in-house stay will involve collection of blood samples for pharmacokinetic (PK) analysis. Subjects will stay for a minimum of 24 hours after initial dosing. A dose-escalation schema has been chosen to maximise safety for participants based on preclinical toxicology studies. The pre-defined dose levels are: 0.1 mg/kg, 1.0 mg/kg, 10.0 mg/kg, 20.0 mg/kg, 30.0 mg/kg. The dosing scheme will consist of a single fixed-dose intravenous infusion of NNZ-2566 over 10 minutes. Dose escalation is subject to the Data Safety Monitoring Committee's (DSMC's) recommendation. A review time period of two to three weeks from end of dosing of each cohort is estimated to enable PK analysis prior to starting the next cohort. The study design precludes intra-subject dose-escalation.

Subjects will then return to the unit on day 7 for an exit evaluation, which will include collection of additional blood samples for safety laboratory testing and safety monitoring.

Intervention type

Drug

Phase

Phase I

Drug names

NNZ-2566

Primary outcome measures

To determine the safety and tolerability of a single intravenous dose of NNZ 2566 when administered as a 10-minute infusion.

Secondary outcome measures

To determine the single dose pharmacokinetics of NNZ 2566 after a 10-minute infusion.

Overall trial start date

15/05/2006

Overall trial end date

15/10/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged between 18 years and 50 years (inclusive)2. Male only: males must also agree to use adequate contraceptive precautions (unless the subject is surgically sterilised) for the duration of the study and for at least 30 days thereafter3. Body mass index (BMI) of 18 to 30 kg/m^24. Healthy - this will be determined by a medical history with particular attention to:4.1. A drug history identifying any known drug allergies and the presence of drug abuse4.2. Any chronic use of medication4.3. A thorough review of body systems. This will also be determined by having no clinically significant abnormal findings on physical examination, which includes an electrocardiogram (ECG), which in the opinion of the investigator would jeopardise the safety of the subject or impact on the validity of the study results5. Volunteers with adequate venous access in their left and right arm to allow collection of blood samples and drug administration6. Fluency in the English language7. Have voluntarily given written informed consent to participate in this study

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

35 males

Participant exclusion criteria

1. History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations (including lactose intolerance). A known hypersensitivity to lidocaine or any surgical dressing which may be used in the study procedures.2. Medical conditions:2.1. History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders2.2. Any history of asthma during the last 10 years2.3. A creatinine clearance of less than 75 ml/min calculated using Cockroft and Gault Formula2.4. Any predisposing condition that might interfere with the absorption, distribution, metabolism, and/or excretion of drugs2.5. History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation2.6. History of hepatitis B, a positive test for hepatitis B surface antigen, a history of hepatitis C, a positive test for hepatitis C antibody, a history of human immunodeficiency virus (HIV) infection or demonstration of HIV antibodies3. Any evidence of organ dysfunction, or any clinically significant clinical laboratory value which, in the opinion of the investigator would jeopardise the safety of the subject or impact on the validity of the study results, including a liver function test (LFT) greater than 1.5 x upper limit of normal (ULN)4. Those who may have difficulty abstaining from alcohol during the 48 hours prior to dose administration and until completion of blood sampling on day 75. History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or positive urine drug screen for drugs of abuse6. Medication:6.1. Difficulty in abstaining from any prescription medications for 14 days prior to dose administration and for the duration of the study6.2. Difficulty in abstaining from over-the-counter (OTC) medications or herbal supplements for 14 days prior to dose administration and for the duration of the study, (with the exception of occasional analgesia, vitamin and other nutrient supplement use, at the discretion of the investigator)7. Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines (e.g., coffee, tea, cola and chocolate) during the 24 hours prior to dose administration and whilst confined at the clinical facility8. History of any psychiatric illness which may impair the ability to provide written informed consent9. Poor compliers or those unlikely to attend10. Receipt of any drug as part of a research study within 30 days of initial dose administration in this study11. Standard blood donation (usually 550 ml) within the 12-week period before dose administration12. Unusual dietary habits, including vegetarian diets and excessive or unusual vitamin intakes13. Vaccination or immunisation within 30 days of initial dose administration